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ALK Gene Mutation and ALK Protein Expression in Advanced Neuroblastoma and the Potential Value in Risk Stratification
Neha Bhardwaj1, Manish Rohilla1, Upasana Gautam1
1Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Objectives:
The protein ALK is targeted for therapy in neuroblastoma, and ALK mutation confers a poor prognosis. We evaluated ALK in a cohort of patients with advanced neuroblastoma diagnosed by fine-needle aspiration biopsy (FNAB).
Methods:
Fifty-four cases of neuroblastoma were evaluated for ALK protein expression by immunocytochemistry and ALK gene mutation by next-generation sequencing. MYCN amplification by fluorescence in situ hybridization, International Neuroblastoma Risk Group (INRG) staging, and risk assignment was performed, and patients were managed accordingly. All parameters were correlated with overall survival (OS).
Results:
ALK protein showed cytoplasmic expression in 65% cases and did not correlate with MYCN amplification (P = .35), INRG groups (P = .52), and OS (P = .2); however, ALK-positive, poorly differentiated neuroblastoma showed better prognosis (P = .02). ALK negativity was associated with poor outcome by Cox proportional hazard model (hazard ratio, 2.36). Two patients showed ALK gene F1174L mutation with 8% and 54% allele frequency and high ALK protein expression; they died of disease 1 and 17 months following diagnosis, respectively. A novel IDH1 exon 4 mutation was also detected.
Conclusions:
ALK expression is a promising prognostic and predictive marker in advanced neuroblastoma that can be evaluated in cell blocks from FNAB samples along with traditional prognostic parameters. ALK gene mutation confers a poor prognosis for patients with this disease.
